BTK degraders induce potent and sustained BTK degradation dependent on CRBN, neddylation, and the proteasome. (A) Immunoblots from Ramos B cells treated as indicated for 4 hours. (B) Immunoblots from Ramos B cells pretreated with the indicated compounds (1 μM) for 4 hours followed by stimulation with α-immunoglobulin M (10 μg/mL) for 30 minutes. (C) Immunoblots from Ramos B cells treated for 2 hours with indicated compounds, followed by washout for indicated times. (D) Immunoblots from Ramos B cells pretreated for 1 hour with bortezomib (500 nM), MLN4924 (1 μM), lenalidomide (10 μM), or CGI1746 (10 μM) and then treated with either DD-03-007 or DD-03-171 (100 nM) for 4 hours. DMSO, dimethyl sulfoxide; IgM, immunoglobulin M; UT, untreated.